Aspirin inhibits TNFα- and IL-1-induced NF-κB activation and sensitizes HeLa cells to apoptosis
Aspirin inhibits TNFα- and IL-1-induced NF-κB activation and sensitizes HeLa cells to apoptosis
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DOI：
10.1016/j.cyto.2003.11.007
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发表时间：
2004-03-07
期刊：
影响因子：
3.8
通讯作者：
Basaga, H
中科院分区：
文献类型：
--
作者：
Kutuk, O;Basaga, H
Rel/核因子-κ B（NF-κ B）转录因子参与调节增殖、凋亡和细胞生长的若干靶基因的转录。TNF α和IL-1诱导的NF-κ B活化途径主要涉及IkappaB α的磷酸化和降解，随后是NF-κ B的核转位和靶基因表达。NF-κ B介导细胞死亡和存活之间的平衡，因为具有相当组成性或诱导性的NF-κ B活化的大多数癌细胞即使通过强凋亡剂如TNF α也对凋亡具有抗性。在这项研究中，我们证明了促炎细胞因子TNF α和IL-1诱导人宫颈癌HeLa细胞中NF-κ B活化。我们的研究表明，乙酰水杨酸（阿司匹林）通过抑制IkappaB α和IkappaB β的磷酸化和降解，以剂量依赖性方式阻止TNF α和IL-1诱导的NF-κ B活化。此外，阿司匹林使HeLa细胞对TNF α诱导的凋亡敏感。这些结果表明，阿司匹林可用于增强基于TNFa的治疗干预在癌症治疗中的有效性。(C)2004 Elsevier Ltd.保留所有权利。
Rel/nuclear factor-kappa B (NF-kappaB) transcription factors are involved in transcription of several target genes that modulate proliferation, apoptosis and cell growth. TNFalpha- and IL-1-induced NF-kappaB activation pathways mainly involve the phosphorylation and degradation of IkappaBalpha by a signalsome complex followed by nuclear translocation of NF-kappaB and target gene expression. NF-kappaB mediates the balance between cell death and survival as most cancer cells that have rather constitutive or inducible activation of NFkappaB are resistant to apoptosis even by strong apoptotic agents such as TNFalpha. In this study we demonstrate that proinfammatory cytokines TNFalpha and IL-1 induced NF-kappaB activation in human cervical carcinoma HeLa cells. Our studies reveal that acetylsalicylic acid (aspirin) prevents TNFalpha- and IL-1-induced NF-kappaB activation in a dose-dependent manner through inhibition of phosphorylation and degradation of IkappaBalpha and IkappaBbeta. Moreover, aspirin sensitizes HeLa cells to TNFalpha-induced apoptosis. These results suggest that aspirin could be used to potentiate the effectiveness of TNFalpha-based therapeutic interventions in cancer treatment. (C) 2004 Elsevier Ltd. All rights reserved.